miR-199a-5p Plays a Pivotal Role on Wound Healing via Suppressing VEGFA and ROCK1 in Diabetic Ulcer Foot

Abstract

Diabetes mellitus (DM) is a growing health problem. As a common complication of DM, diabetic foot ulcer (DFU) results in delayed wound healing and is a leading cause of nontraumatic amputation. miR-199a-5p, a short noncoding RNA, had abnormal expression in DFU wound tissues. The expression of miR-199a-5p was significantly increased in DFU wound tissues, skin tissues of diabetic rats, and high glucose-induced cells. Vascular endothelial growth factor A (VEGFA) and Rho-associated kinase 1 (ROCK1) are directly targets of miR-199a-5p. Inhibiting the expression of miR-199a-5p alleviated the inhibition of VEGFA and ROCK1, thereby rescued impaired proliferation and migration of HG-induced cells, and restored the normal function of the cells to some extent. In diabetic rats, inhibition of miR-199a-5p significantly increased the expression of VEGFA and ROCK1, significantly promoted wound healing, and rescued impaired wound healing. miR-199a-5p and its targets showed therapeutic effect on diabetic wounds.

Effects of Intensive Glycemic Control on Serum Exosome miR‐126‐3p and miR‐125b‐1‐3p Levels and Wound Healing in Patients with Diabetic Ulcers

“…Several studies have confrmed that many miRNAs participate in the process of wound healing [26][27][28][29]. During the infammatory period of the wound, miRNA-181c and miRNA-21-5p promote the expression of M2 macrophages to inhibit the infammatory response and shorten the infammatory response time [30,31].…”

Effect and mechanism of microRNAs on various diabetic wound local cells

“…By directly targeting VEGFA and Rho-associated kinase 1 (ROCK1), it leads to decreased proliferation and migration of ECs. 46 In diabetic rats, inhibition of miR-199a-5p significantly increased the expression of VEGFA and ROCK1, thus promoting wound healing. Therefore, miR-199a-5p and its targets have a significant therapeutic effect on diabetic wounds.…”

“…Therefore, miR-199a-5p and its targets have a significant therapeutic effect on diabetic wounds. 46 Compared with normal mice, miR-31-5p was significantly reduced in the full-thickness wound of diabetic mice, and its target HIF1AN was inadequate, which led to the deficiency of EC proliferation, migration, and tube formation. 38 By using milk exosomes loaded with miR-31-5p mimics, the research team effectively improved the function of ECs in vitro and also promoted wound blood vessel formation and wound healing in this way.…”

Non-coding RNAs: Role in diabetic foot and wound healing

“…Huang et al [ 47 ] found that miR-489-3p downregulation increases sirtuin (SIRT) 1 expression, promotes the PI3K/AKT/eNOS signaling pathway, improves cellular antioxidant capacity, and alleviates DFU. MiR-199a-5p has an important role in the development of diabetes and its complications[ 48 , 49 ]. Moreover, miR-199a-5p promotes apoptosis and ROS production within pancreatic β-cells in type 2 DM (T2DM)[ 50 ].…”

“…MiR-199a-5p sponge-adsorbed to hsa-circ-006040 inhibits macrophage-mediated inflammatory responses in type 1 DM (T1DM)[ 48 ]. Wang et al [ 49 ] found that downregulating miR-199a-3p in endothelial cells alleviates inhibition of the target VEGFA and Rho-related kinase 1, rescuing the cellular damage induced by high glucose and restoring angiogenic function. Therefore, these findings suggest that regulating miRNA expression during the proliferative phase of wound healing has great potential in DFU treatment and wound repair.…”